This project is concerned with the functions of the exocrine pancreas. We are particularly interested in the mechanisms at work in the transport of digestive enzyme within and out of the pancreatic acinar cell. In addition, the project will study how these processes are regulated. The studies on digestive enzyme secretion include investigations on the intracellular transport of digestive enzymes; the assembly, structure and secretory role (fusion, cycling, and capacitive function) of the zymogen granule; and digestive enzyme transport into and out of cells via non-granular pathways involving the direct transport of individual molecules across cell membranes. Also included are studies in which the regulation of digestive enzyme synthesis and transport by the end-products of digestion (amino acids, monosaccharides etc.) will be examined to evaluate their role in the overall regulation of secretion and digestion. In addition, studies on pancreatic ion transport will investigate the mechanisms involved in ion transport across the major electrolyte and water secreting surfaces of the pancreas. The action of the hormone secretin, on these processes will also be studied. A better understanding of normal pancreatic function, particularly at the cellular and subcellular level, is prerequisite for understanding and treating disorders of this gland including acute and chronic pancreatitis, carcinoma of the pancreas, and cystic fibrosis of the pancreas.